An emerging trend in neuroscience and neurophysiology is the movement towards understanding the fundamental behavior of neurons at the ensemble or population level by studying individual neurons at multiple sites. Electrophysiology of populations of neurons is greatly aided by the development of multi-channel or array electrodes by integrated circuit (IC) technology. However, there is considerable heterogeneity in the distribution and function of neurochemical elements as well. Therefore, a technology that enables simultaneous monitoring of neurochemical activity at different locations in the brain promises to make fundamental discoveries in regional heterogeneity and specialization of neurochemistry of brain tissue. Further, if the electrical activity of a population of neurons as well as the complementary neurotransmitter activity could be localized and measured concurrently, it could unify two important domains: electrophysiology and neurochemistry/pharmacology. The central goal of this proposal is to develop a novel microsensor technology for providing real time, continuous measurement of both neurotransmitter and neuronal electrical activity. The underlying novel idea is to construct a carbon-based microsensor array that will capture neurotransmitter and electrical activity from multiple neurons. Specifically, the microsensor array will be developed for measuring the diffusible messenger nitric oxide (NO) and the neuronal electrical response accompanying NO activity. The sensor will be tested in an in vitro model (hippocampai brain slice) in which the distribution of NO and its role in modulating the excitability of neurons in different regions of the slice will be studied. Fundamental technical barriers that must be overcome are: 1) Development of a carbon-based microsensor technology by utilizing novel screen printing and photolithographic processing techniques. 2) Combining electrical and electrochemical sensing on a single substrate and interfacing this sensor array to the brain tissue. This technology offers a revolutionary advance in neurophysiology research: it will potentially break down the barrier that exists in neuroscience, between the fields of pharmacological neuroscience and electrophysiologic neuroscience. The coupling of these two basic neural responses, electrical and chemical, would shift the prevailing paradigm of neuroscience research pertaining to neurological diseases or mental health.